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A knowledge integration strategy for the selection of a robust multi-stress biomarkers panel for Bacillus subtilis

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Synthetic and Systems Biotechnology 2023年第1期8卷 97-106页

作者： Yiming Huang Nishant Sinha Anil Wipat Jaume Bacardit interdisciplinary Computing and Complex biosystems(ICOS)Group School of ComputingNewcastle UniversityUK Department of Neurology Perelman School of MedicineUniversity of PennsylvaniaUSA

One challenge in the engineering of biological systems is to be able to recognise the cellular stress states of bacterial hosts,as these stress states can lead to suboptimal growth and lower yields of target *** enable the design of genetic circuits for reporting or mitigating the stress states,it is important to identify a relatively reduced set of gene biomarkers that can reliably indicate relevant cellular growth states in *** advances in high-throughput omics technologies have enhanced the identification of molecular biomarkers specific states in bacteria,motivating computational methods that can identify robust biomarkers for experimental characterisation and *** on identifying gene expression biomarkers to sense various stress states in Bacillus subtilis,this study aimed to design a knowledge integration strategy for the selection of a robust biomarker panel that generalises on external datasets and *** developed a recommendation system that ranks the candidate biomarker panels based on complementary information from machine learning model,gene regulatory network and co-expression *** identified a recommended biomarker panel showing high stress sensing power for a variety of conditions both in the dataset used for biomarker identification(mean f1-score achieved at 0.99),as well as in a range of independent datasets(mean f1-score achieved at 0.98).We discovered a significant correlation between stress sensing power and evaluation metrics such as the number of associated regulators in a *** gene regulatory network(GRN)and the number of associated modules in a *** co-expression network(CEN).GRNs and CENs provide information relevant to the diversity of biological processes encoded by biomarker *** demonstrate that quantitatively relating meaningful evaluation metrics with stress sensing power has the potential for recognising biomarkers that show better sensitivity and robustness to an exte

关键词： Transcriptomics analysis System biology Biomarker discovery Machine learning

Therapeutic strategies of three-dimensional stem cell spheroids and organoids for tissue repair and regeneration

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Bioactive Materials 2023年第1期19卷 50-74页

作者： Woochan Kim Yonghyun Gwon Sunho Park Hyoseong Kim Jangho Kim Department of Convergence biosystems Engineering Chonnam National UniversityGwangju61186Republic of Korea Department of Rural and biosystems Engineering Chonnam National UniversityGwangju61186Republic of Korea interdisciplinary Program in IT-Bio Convergence System Chonnam National UniversityGwangju61186Republic of Korea

Three-dimensional(3D)stem cell culture systems have attracted considerable attention as a way to better mimic the complex interactions between individual cells and the extracellular matrix(ECM)that occur in ***,3D cell culture systems have unique properties that help guide specific functions,growth,and processes of stem cells(e.g.,embryogenesis,morphogenesis,and organogenesis).Thus,3D stem cell culture systems that mimic in vivo environments enable basic research about various tissues and *** this review,we focus on the advanced therapeutic applications of stem cell-based 3D culture systems generated using different engineering ***,we summarize the historical advancements of 3D cell culture systems and discuss the therapeutic applications of stem cell-based spheroids and organoids,including engineering techniques for tissue repair and regeneration.

关键词： 3D stem cell culture Spheroid Organoid Tissue repair Tissue regeneration

Understanding cell-extracellular matrix interactions for topology-guided tissue regeneration

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BIOCELL 2023年第4期47卷 789-808页

作者： AAYUSHI RANDHAWA SAYAN DEB DUTTA KEYA GANGULY TEJAL V.PATIL RACHMI LUTHFIKASARI KI-TAEK LIM Department of biosystems Engineering Kangwon National UniversityChuncheon24341Korea interdisciplinary Program in Smart Agriculture Kangwon National UniversityChuncheon24341Korea

Tissues are made up of cells and the extracellular matrix(ECM)which surrounds *** cells and tissues are actively adaptable to enduring significant stress that occurs in daily *** astonishing mechanical stress develops due to the interaction between the live cells and the non-living *** in the matrix microenvironment can sense the signals and forces produced and initiate a signaling cascade that plays a crucial role in the body’s normal functioning and influences various properties of the native cells,including growth,proliferation,and ***,the matrix’s characteristic features also impact the repair and regeneration of the damaged *** current study reviewed how the cell-ECM interaction regulates cellular behavior and physicochemical ***,we have described the response of cells to mechanical stresses,the importance of substrate stiffness and geometry in tissue regeneration,and the development of scaffolds to mimic the nature of native ECM in 3D for tissue engineering applications has also been ***,the study summarizes the conclusions and promising prospects based on the cell-ECM interplay.

关键词： ECM Stress Mechanical force Scaffold Mechanotransduction Tissue engineering

Transformer2 proteins protect breast cancer cells from accumulating replication stress by ensuring productive splicing of checkpoint kinase 1

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Frontiers of Chemical Science and Engineering 2016年第2期10卷 186-195页

作者： Andrew Best Katherine James Gerald Hysenaj Alison Tyson-Capper David J. Elliott Institute of Genetic Medicine Newcastle University Newcastle NE1 3BZ UK interdisciplinary Computing and Complex biosystems research Group and centre for Bacterial Cell Biology Newcastle University Newcastle NE1 3BZ UK Institute for Cellular Medicine Newcastle University Newcastle NE2 4HH UK

Increased expression levels of the RNA splicing regulator Transformer2fl （abbreviated Tra2fl） have been reported in several types of cancer. Recent work has revealed an intimate cross-regulation between Tra2fl and the highly similar Tra2a protein in human breast cancer cells, though these two proteins are encoded by separate genes created by a gene duplication that occurred over 500 million years ago. This cross-regulation involves splicing control of a special class of exons, called poison exons. Down-regulation of Tra2fl reduces splicing inclu- sion of a poison exon in the mRNA encoding Tra2a, thereby up-regulating Tra2a protein expression. This buffers any splicing changes that might be caused by individual depletion of Tra2fl alone. Discovery of this cross-regulation pathway, and its by-pass by joint deple- tion of both human Tra2 proteins, revealed Tra2 proteins are essential for breast cancer cell viability, and led to the identification of important targets for splicing control. These exons include a critical exon within the checkpoint kinase 1 （CHK1） gene that plays a crucial function in the protection of cancer cells from replication stress. Breast cancer cells depleted for Tra2 proteins have reduced CHK1 protein levels and accumulate DNA damage. These data suggest Tra2 proteins and/or their splicing targets as possible cancer drug targets.

关键词： RNA splicing gene expression breast cancer,DNA damage CHK1

Unraveling the potential of 3D bioprinted immunomodulatory materials for regulating macrophage polarization:State-of-the-art in bone and associated tissue regeneration

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Bioactive Materials 2023年第10期28卷 284-310页

作者： Sayan Deb Dutta Tejal V.Patil Keya Ganguly Aayushi Randhawa Ki-Taek Lim Department of biosystems Engineering Kangwon National UniversityChuncheon24341Republic of Korea Institute of Forest Science Kangwon National UniversityChuncheon24341Republic of Korea interdisciplinary Program in Smart Agriculture Kangwon National UniversityChuncheon24341Republic of Korea

Macrophage-assisted immunomodulation is an alternative strategy in tissue engineering, wherein the interplay between pro-inflammatory and anti-inflammatory macrophage cells and body cells determines the fate of healing or inflammation. Although several reports have demonstrated that tissue regeneration depends on spatial and temporal regulation of the biophysical or biochemical microenvironment of the biomaterial, the underlying molecular mechanism behind immunomodulation is still under consideration for developing immunomodulatory scaffolds. Currently, most fabricated immunomodulatory platforms reported in the literature show regenerative capabilities of a particular tissue, for example, endogenous tissue (e.g., bone, muscle, heart, kidney, and lungs) or exogenous tissue (e.g., skin and eye). In this review, we briefly introduced the necessity of the 3D immunomodulatory scaffolds and nanomaterials, focusing on material properties and their interaction with macrophages for general readers. This review also provides a comprehensive summary of macrophage origin and taxonomy, their diverse functions, and various signal transduction pathways during biomaterial-macrophage interaction, which is particularly helpful for material scientists and clinicians for developing next-generation immunomodulatory scaffolds. From a clinical standpoint, we briefly discussed the role of 3D biomaterial scaffolds and/or nanomaterial composites for macrophage-assisted tissue engineering with a special focus on bone and associated tissues. Finally, a summary with expert opinion is presented to address the challenges and future necessity of 3D bioprinted immunomodulatory materials for tissue engineering.

关键词： Macrophage Immunomodulation Biomaterials 3D bioprinting Tissue engineering

Bioinspired magnetic cilia:from materials to applications

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Microsystems & Nanoengineering 2023年第6期9卷 107-128页

作者： Seongjin Park Geonjun Choi Minsu Kang Woochan Kim Jangho Kim Hoon Eui Jeong Department of Mechanical Engineering Ulsan National Institute of Science and Technology(UNIST)Ulsan44919Republic of Korea Department of Convergence biosystems Engineering Chonnam National UniversityGwangju61186Republic of Korea interdisciplinary Program in IT-Bio Convergence System Chonnam National UniversityGwangju61186Republic of Korea

Microscale and nanoscale cilia are ubiquitous in natural systems where they serve diverse biological *** artificial magnetic cilia have emerged as a highly promising technology with vast potential applications,ranging from soft robotics to highly precise *** this review,we comprehensively discuss the roles of cilia in nature and the various types of magnetic particles utilized in magnetic cilia;additionally,we explore the top-down and bottom-up fabrication techniques employed for their ***,we examine the various applications of magnetic cilia,including their use in soft robotics,droplet and particle control systems,fluidics,optical devices,and ***,we present our conclusions and the future outlook for magnetic cilia research and development,including the challenges that need to be overcome and the potential for further integration with emerging technologies.

关键词： magnetic overcome precise

Wet tissue adhesive polymeric powder hydrogels for skeletal muscle regeneration

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Bioactive Materials 2024年第10期40卷 334-344页

作者： Mingyu Lee Daun Seo Junggeon Park Sun Hong Lee Jin Jeon Woochan Kim Jangho Kim Hee Seok Yang Jae Young Lee School of Materials Science and Engineering Gwangju Institute of Science and TechnologyGwangju61005Republic of Korea Department of Nanobiomedical Science&BK21 FOUR NBM Global research Center for Regenerative Medicine Dankook UniversityCheonan31116Republic of Korea Department of Convergence biosystems Engineering Chonnam National UniversityGwangju61186Republic of Korea Department of Rural and biosystems Engineering Chonnam National UniversityGwangjuRepublic of Korea interdisciplinary Program in IT-Bio Convergence System Chonnam National UniversityGwangju61186Republic of Korea

Volumetric muscle loss(VML)frequently results from traumatic incidents and can lead to severe functional *** have been widely employed for VML tissue regeneration,which are unfortunately ineffective because of the lack of intimate contact with injured tissue for structural and mechanical *** hydrogels allow for strong tissue connections for wound ***,conventional adhesive hydrogels exhibit poor tissue adhesion in moist,bleeding wounds due to the hydration layer at the tissue–hydrogel interfaces,resulting in insufficient *** this study,we developed a novel,biocompatible,wet tissue adhesive powder hydrogel consisting of dextran-aldehyde(dex-ald)and gelatin for the regeneration of *** powder absorbs the interfacial tissue fluid and buffer solution on the tissue,spontaneously forms a hydrogel,and strongly adheres to the tissue via various molecular interactions,including the Schiff base *** particular,the powder composition with a 1:4 ratio of dex-ald to gelatin exhibited optimal characteristics with an appropriate gelation time(258 s),strong tissue adhesion(14.5 kPa),and ***-ald/gelatin powder hydrogels presented strong adhesion to various organs and excellent hemostasis compared to other wet hydrogels and fibrin glue.A mouse VML injury model revealed that the dex-ald/gelatin powder hydrogel significantly improved muscle regeneration,reduced fibrosis,enhanced vascularization,and decreased ***,our wet-adhesive powder hydrogel can serve as an effective platform for repairing various tissues,including the heart,muscle,and nerve tissues.

关键词： Powder Hydrogel Wet-adhesive Skeletal muscle regeneration

Front line defenders of the ecological niche!Screening the structural diversity of peptaibiotics from saprotrophic and fungicolous Trichoderma/Hypocrea species

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Fungal Diversity 2014年第6期69卷 117-146页

作者： Christian R.Rohrich Walter M.Jaklitsch Hermann Voglmayr Anita Iversen Andreas Vilcinskas Kristian Fog Nielsen Ulf Thrane Hans von Dohren Hans Bruckner Thomas Degenkolb Bioresources Project Group Fraunhofer Institute for Molecular Biology and Applied Ecology(IME)Winchesterstrasse 235394 GiessenGermany Department of Systematic and Evolutionary Botany Faculty Centre of BiodiversityUniversity of ViennaRennweg 141030 ViennaAustria Department of Systems Biology Technical University of DenmarkSoltofts PladsBuilding 2212800 Kgs.LyngbyDenmark interdisciplinary research centre for biosystems Land Use and Nutrition(IFZ)Department of Applied EntomologyInstitute of Phytopathology and Applied Zoology(IPAZ)University of GiessenHeinrich-Buff-Ring 26-3235392 GiessenGermany Biochemistry and Molecular Biology OE 2 Institute of ChemistryTechnical University of BerlinFranklinstrasse 2910587 BerlinGermany interdisciplinary research centre for biosystems Land Use and Nutrition(IFZ)Department of Food SciencesInstitute ofNutritional ScienceUniversity of GiessenHeinrich-Buff-Ring 26-3235392 GiessenGermany AB SCIEXGermany GmbH Landwehrstrasse 5464293 DarmstadtGermany Danish Emergency Management Agency Universitetsparken 22100 CopenhagenDenmark

Approximately 950 individual sequences of nonribosomally biosynthesised peptides are produced by the genus Trichoderma/Hypocreathat belong to a perpetually growing class of mostly linear antibiotic oligopeptides,which are rich in the non-proteinogenic α-aminoisobutyric acid(Aib).Thus,they are comprehensively named ***,peptaibiotics represent ca.80% of the total inventory of secondarymetabolites currently known from Trichoderma/*** unique membrane-modifying bioactivity results from amphipathicity and helicity,thus making them ideal candidates in assisting both colonisation and defence of the natural habitats by their fungal *** this,reports on the in vivo-detection of peptaibiotics have scarcely been published in the *** order to evaluate the significance of peptaibiotic production for a broader range of potential producers,we screened nine specimens belonging to seven hitherto uninvestigated fungicolous or saprotrophic Trichoderma/Hypocrea species by liquid chromatography coupled to electrospray high resolution mass *** of peptaibiotics found were independently confirmed by analysing the peptaibiome of pure agar cultures obtained by single-ascospore isolation from the *** the nine species examined,five were screened positive for peptaibiotics.A total of 78 peptaibiotics were sequenced,56(=72%)of which are ***,dihydroxyphenylalaninol and O-prenylated tyrosinol,two C-terminal residues,which have not been reported for peptaibiotics before,were found as well as new and recurrent sequences carrying the recently described tyrosinol residue at their *** majority of peptaibiotics sequenced are 18-or 19-residue *** homologies with‘classical representatives’of subfamily 1(SF1)-peptaibiotics argue for the formation of transmembrane ion channels,which are prone to facilitate the producer capture and defence of its substratum.

关键词： HPLC/QTOF-ESI-HRMS Metabolite profiling Peptaibiotics Peptaibols Aib peptides Trichoderma Hypocrea

Nanocellulose,a versatile platform:From the delivery of active molecules to tissue engineering applications

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Bioactive Materials 2022年第3期7卷 566-589页

作者： Tejal V.Patil Dinesh K.Patel Sayan Deb Dutta Keya Ganguly Tuhin Subhra Santra Ki-Taek Lim Department of biosystems Engineering Institute of Forest ScienceKangwon National UniversityChuncheon24341Republic of Korea interdisciplinary Program in Smart Agriculture Kangwon National UniversityChuncheon24341Republic of Korea Deptarment of Engineering Design Indian Institute of TechnologyMadras600036India

Nanocellulose,a biopolymer,has received wide attention from researchers owing to its superior physicochemical properties,such as high mechanical strength,low density,biodegradability,and *** can be extracted from wide range of sources,including plants,bacteria,and *** on the extraction process and dimensions(diameter and length),they are categorized into three main types:cellulose nanocrystals(CNCs),cellulose nanofibrils(CNFs),and bacterial nanocellulose(BNC).CNCs are a highly crystalline and needle-like structure,whereas CNFs have both amorphous and crystalline regions in their *** is the purest form of *** nanocellulose properties can be tuned by chemical functionalization,which increases its applicability in biomedical *** review highlights the fabrication of different surface-modified nanocellulose to deliver active molecules,such as drugs,proteins,and ***-mediated delivery of active molecules is profoundly affected by its topographical structure and the interaction between the loaded molecules and *** applications of nanocellulose and its composites in tissue engineering have been ***,the review is concluded with further opportunities and challenges in nanocellulose-mediated delivery of active molecules.

关键词： Nanocellulose Chemical functionalization Drug delivery Protein delivery Plasmid delivery Tissue engineering